Viral vectors transduce genes into target cells with high efficiencies owing to specific virus envelope-host cell receptor interaction and viral mechanisms for gene expression. Consequently, viral vectors have been used as vehicles for the transfer of genes into many different cell types. The ability to introduce and express a foreign gene in a cell is useful for the study of gene expression and the elucidation of cell lineages. Retroviral vectors, capable of integration into the cellular chromosome, have also been used for the identification of developmentally important genes via insertional mutagenesis. Viral vectors, and retroviral vectors in particular, are also used in therapeutic applications (e.g., gene therapy), in which a gene (or genes) is added to a cell to replace a missing or defective gene due to an inherited or acquired condition or to inactivate a pathogen such as a virus.
In view of the wide variety of potential genes available for therapy, it is clear that an efficient means of delivering these genes is needed in order treat infectious, as well as non-infectious diseases. Factors affecting viral vector usage include tissue tropism, stability of virus preparations, genome packaging capacity, and construct-dependent vector stability. In addition, in vivo application of viral vectors is often limited by host immune responses against viral structural proteins and/or transduced gene products.
Lymphocytic choriomeningitis virus was the first member of the arenavirus family identified, originally isolated in a sample from an outbreak of St. Louis encephalitis in 1933 (Buchmeier et al., “Arenaviridae: The Viruses and Their Replication.” In: Knipe D M, Howley P M, eds. Fields Virology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001:1635-1668). The virus is endemic in rodents, which serve as a reservoir. LCMV is generally noncytopathic and the most common human disease associated with LCMV is aseptic meningitis. A characteristic feature of infection with wild type LCMV is widespread infection of epithelial tissues (Buchmeier et al., supra). Of interest, there is evidence to suggest that LCMV may be spread by inhalation of infected material [Kenyon et al., Intervirology, 33:23-31 (1992)].